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      Sporadic multiple parathyroid gland disease—a consensus report of the European Society of Endocrine Surgeons (ESES)

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          Abstract

          Background

          Sporadic multiglandular disease (MGD) has been reported in literature in 8–33 % of patients with primary hyperparathyroidism (pHPT). This paper aimed to review controversies in the pathogenesis and management of sporadic MGD.

          Methods

          A literature search and review was made to evaluate the level of evidence concerning diagnosis and management of sporadic MGD according to criteria proposed by Sackett, with recommendation grading by Heinrich et al. and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Results were discussed at the 6th Workshop of the European Society of Endocrine Surgeons entitled ‘Hyperparathyroidism due to multiple gland disease: An evidence-based perspective’.

          Results

          Literature reports no prospective randomised studies; thus, a relatively low level of evidence was achieved. Appropriate surgical therapy of sporadic MGD should consist of a bilateral approach in most patients. Unilateral neck exploration guided by preoperative imaging should be reserved for selected patients, performed by an experienced endocrine surgeon and monitored by intraoperative parathormone assay (levels of evidence III–V, grade C recommendation). There is conflicting or equally weighted levels IV–V evidence supporting that cure rates can be similar or worse for sporadic MGD than for single adenomas (no recommendation). Best outcomes can be expected if surgery is performed by an experienced parathyroid surgeon working in a high-volume centre (grade C recommendation). Levels IV–V evidence supports that recurrent/persistence pHPT occurs more frequently in patients with double adenomas hence in situations where a double adenoma has been identified, the surgeon should have a high index of suspicion during surgery and postoperatively for the possibility of a four-gland disease (grade C recommendation).

          Conclusions

          Identifying preoperatively patients at risk for MGD remains challenging, intraoperative decisions are important for achieving acceptable cure rates and long-term follow-up is mandatory in such patients.

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          Most cited references 111

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          Guidelines for diagnosis and therapy of MEN type 1 and type 2.

          This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.
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            Rules of evidence and clinical recommendations on the use of antithrombotic agents.

             D.L. Sackett (1989)
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              Anti-bipolar therapy: mechanism of action of lithium.

               Richard Jope (1999)
              This review introduces the concepts that multiple actions of lithium are critical for its therapeutic effect, and that these complex effects stabilize neuronal activities, support neural plasticity, and provide neuroprotection. Three interacting systems appear most critical. (i) Modulation of neurotransmitters by lithium likely readjusts balances between excitatory and inhibitory activities, and decreased glutamatergic activity may contribute to neuroprotection. (ii) Lithium modulates signals impacting on the cytoskeleton, a dynamic system contributing to neural plasticity, at multiple levels, including glycogen synthase kinase-3beta, cyclic AMP-dependent kinase, and protein kinase C, which may be critical for the neural plasticity involved in mood recovery and stabilization. (iii) Lithium adjusts signaling activities regulating second messengers, transcription factors, and gene expression. The outcome of these effects appears likely to result in limiting the magnitudes of fluctuations in activities, contributing to a stabilizing influence induced by lithium, and neuroprotective effects may be derived from its modulation of gene expression.
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                Author and article information

                Contributors
                0048 12 633 1995 , marbar@mp.pl
                Journal
                Langenbecks Arch Surg
                Langenbecks Arch Surg
                Langenbeck's Archives of Surgery
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1435-2443
                1435-2451
                5 November 2015
                5 November 2015
                2015
                : 400
                : 887-905
                Affiliations
                [ ]Department of Endocrine Surgery, Third Chair of General Surgery, Jagiellonian University Medical College, 37 Prądnicka Street, 31-202 Kraków, Poland
                [ ]Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
                [ ]First Division of Surgery, Research Center for Endocrine Surgery, University of Insubria School of Medicine, Varese, Italy
                [ ]Department of Endocrine Surgery, Oxford University Hospitals NHS Trust, Oxford, UK
                Article
                1348
                10.1007/s00423-015-1348-1
                4747992
                26542689
                © The Author(s) 2015

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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                © Springer-Verlag Berlin Heidelberg 2015

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